Abstract:
:Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy that frequently metastasizes and that overexpresses transforming growth factor-beta s (TGF-beta s). To determine whether TGF-beta s can act to enhance the metastatic potential of PDAC, PANC-1 human pancreatic cancer cells were transfected with an expression construct encoding a soluble type II TGF-beta receptor (sT beta RII) that blocks cellular responsiveness to TGF-beta 1. When injected s.c. in athymic mice, PANC-1 clones expressing sT beta RII exhibited decreased tumor growth in comparison with sham-transfected cells and attenuated expression of plasminogen activator inhibitor 1 (PAI-1), a gene associated with tumor growth. When tested in an orthotopic mouse model, these clones formed small intrapancreatic tumors that exhibited a suppressed metastatic capacity and decreased expression of plasminogen activator inhibitor 1 and the metastasis-associated urokinase plasminogen activator. These results indicate that TGF-beta s act in vivo to enhance the expression of genes that promote the growth and metastasis of pancreatic cancer cells and suggest that sT beta RII may ultimately have a therapeutic benefit in PDAC.
journal_name
Mol Cancer Therjournal_title
Molecular cancer therapeuticsauthors
Rowland-Goldsmith MA,Maruyama H,Matsuda K,Idezawa T,Ralli M,Ralli S,Korc Mkeywords:
subject
Has Abstractpub_date
2002-01-01 00:00:00pages
161-7issue
3eissn
1535-7163issn
1538-8514journal_volume
1pub_type
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